Antibodies directed against idiotypic determinants on anti-Staphylococcal nuclease antibodies from different mouse strains have been produced in rats and in pigs. The idiotypes are detected by hemagglutination assays and by the inhibition of antibody-mediated inactivation of nuclease. By screening a variety of strains and offspring from appropriate matings between strains for the presence of idiotypes and other markers, it has been shown that idiotype expression is linked to the heavy chain allotype markers. A number of recombinants between different idiotype markers have been found and may provide tools for fine-structure mapping of heavy chain variable region genes. Administration of anti-idiotypic antibodies to mice has been found to induce idiotype expression in the serum of these animals. This effect appears to involve T cells, since it is not observed in nude mice, and since evidence for idiotype expression on T helper cells in an in vitro anti-TNP nuclease response has also been obtained using spleens from such treated animals. Isoelectric focusing studies on antinuclease antibodies have indicated characteristic spectrotypes for different strains which appear to correlate with idiotype expression.